(P20-057-25) Characterizing the Effects of Vitamin D Deficiency on the Gut-Liver Axis in the Context of Obesity: An In Vivo Model

Objectives: Obesity and vitamin D (VD) deficiency have been shown to promote the development and progression of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) by disrupting the gut-liver axis. These disruptions, including increased intestinal permeability and metabolic endotoxemia driven by LPS promote liver inflammation and injury. Populations exhibiting both conditions face heightened risk of disease progression due to compounded metabolic and inflammatory effects and impaired immune function at the local and systemic level. This study characterizes these effects on the gut-liver axis in an obese murine model.

Methods: Forty C57/Bl6 male mice were randomized into four conditions for 13 weeks: control diet (10% kcal fat) or high-fat diet (HFD) (60% kcal fat), with either repleted VD (1000 IU) or depleted VD (500 IU). Body weight, total caloric intake, and VD intake were measured weekly. At sacrifice, final body weight, liver weight, adipose weight, and associated ratios were taken. Murine sera, intestinal mucosa, and liver tissues were collected for analysis. Depending on required analysis, either parametric or non-parametric tests were performed.

Results: Diet influenced body weight trends over time with HFD demonstrating highest weight gain when compared to control. At the end of the study, diet influenced liver and adipose weight with HFD demonstrating greater organ weight increases. VD dose influenced liver weight and liver-to-body weight ratio. While both diet type and VD dosing independently influenced liver weight, with diet having the stronger effect, an interaction effect was observed. Additional data will be presented to confirm sera VD status, sera LPS concentrations, and liver injury indicated via sera ALT and AST. Protein expression will be analyzed in the gut mucosa and liver tissue.

Conclusions: While this study is ongoing, characterizing the effects of VD deficiency is important for understanding the underlying mechanisms impacting obese MASLD populations. Diet type and VD, independently or through interaction, influenced murine body weight over the course of this study and liver and adipose weight at the conclusion of this study. Current findings may enable the development of strategies to reverse the impact of VD deficiency and obesity on MASLD progression and outcomes.

Funding Sources: Texas State University